Extremely high prevalence of neural tube defects in a 4-county area in Shanxi Province, China

BACKGROUND: In the past, northern China's Shanxi Province has reported the highest incidence of neural tube defects (NTDs) in the world. However, little is known about the epidemiology of NTDs in this area in recent years. METHODS: Data were collected from a population-based birth defects surveillance system in 4 counties that captures information on all live births, stillbirths of at least 20 weeks' gestation, and pregnancy terminations at any gestational age resulting from prenatal diagnosis of a birth defect. We also surveyed mothers of NTD case patients to determine their use of folic acid before and during early pregnancy. RESULTS: During 2003, 160 NTD cases were identified among 11,534 births (NTD birth prevalence = 138.7/10,000 births). The rates of anencephaly, spina bifida and encephalocele were 65.9, 58.1, and 14.7 per 10,000, respectively, and a female predominance was observed among anencephaly cases (male-to-female relative risk [RR], 0.49; 95% confidence interval [CI], 0.30-0.79), but not among spina bifida (RR, 0.90; 95% CI, 0.55-1.45) and encephalocele (RR, 1.03; 95% CI, 0.40-2.69) cases. The percentages of pregnancy termination following prenatal diagnosis of anencephaly, spina bifida, and encephalocele were 50%, 41.8%, and 35.3%, respectively. NTD birth prevalence tended to be higher among mothers aged <20 or > or =30 years (P = .06) and was markedly associated with lower levels of maternal education (P < .001). Among 143 NTD mothers, only 6 (4.2%) used folic acid supplements during the periconceptional period. CONCLUSIONS: The NTD birth prevalence rate in the study area is among the highest worldwide. Folic acid deficiency may be one important risk factor.     

Maternal flu or fever, medication use, and neural tube defects: a population-based case-control study in Northern China

BACKGROUND: Maternal exposure to flu or fever has been associated with increased risk for neural tube defects (NTDs); however, few studies have considered the effects of medications on the effects of flu or fever. We evaluated the effect of maternal flu or fever, medication use (antibiotics, antipyretics), and their joint effect on NTDs. METHODS: Data came from an ongoing population-based case-control study of infants with external malformations in northern China. The case group included 363 infants with NTDs identified between January 2003 and June 2005. Controls were 523 newborn infants without identified congenital anomalies matched by county, sex, maternal ethnic group, and the closest date of conception for infants with any major external malformation. Data were collected by a trained health worker through face-to-face interviews after delivery. RESULTS: NTD risks were significantly associated with maternal flu or fever (adjusted odds ratio [AOR] = 3.93, 95% CI: 2.48-6.23) and antipyretic use (AOR = 4.86, 95% CI: 1.33-17.78), but not with antibiotic use (AOR = 1.75, 95% CI: 0.91-3.38) after adjusting for potential confounders. NTD risk associated with maternal antipyretic use was markedly higher for anencephaly (AOR = 7.03, 95% CI: 1.70-29.04) than for spina bifida (AOR = 3.98, 95% CI: 0.95-16.74). Mothers with flu or fever who were also using antipyretics showed a markedly higher AOR for anencephaly (14.75 vs. 4.52), spina bifida (16.30 vs. 3.85), and all NTDs combined (13.91 vs. 4.04) than mothers with flu or fever who were not using antipyretics. Maternal antibiotics did not markedly change the effects of flu or fever on anencephaly (4.17 vs. 4.83), spina bifida (5.08 vs. 4.21), and all NTDs combined (5.05 vs. 4.29). CONCLUSIONS: Maternal flu or fever and antipyretic use during the periconceptional period increases the risk for NTDs. Maternal exposure to antipyretics together with flu or fever results in a markedly higher risk of NTDs than exposure to flu or fever alone.     

NTD prevalences in central California before and after folic acid fortification

BACKGROUND: In many regions, NTD prevalences were already declining prior to folic acid fortification. This study examined whether the declining prefortification (1989–1996) NTD prevalences continued into the postfortification period (1998–2003) in selected California counties. METHODS: This population‐based study used vital statistics data and birth defects registry data that were actively ascertained from medical records. The study population included all live births and stillbirths delivered in central California counties from 1989 to 2003. Cases included deliveries with NTDs during the same time period. RESULTS: For all NTDs combined, the slopes indicated that NTD prevalence was decreasing by 7.5 (slope: ?7.5; 95% CI: ?12.4, ?2.5) cases per 100,000 deliveries per year before fortification, whereas NTD prevalence was no longer decreasing after fortification. Comparison of the difference in the two slopes indicated that the postfortification slope exceeded the prefortification slope by 12.6 (95% CI: 2.6, 22.6) cases per 100,000 deliveries per year. CONCLUSIONS: Annual NTD prevalences in central California did not continue to decrease after implementation of folic acid fortification. Birth Defects Research (Part A) 2008. © 2008 Wiley‐Liss, Inc.     

Reduced folate carrier gene is a risk factor for neural tube defects in a Chinese population

BACKGROUND: There is a considerable body of data demonstrating that periconceptional supplementation of folic acid can prevent a significant proportion of neural tube defects (NTDs). At present, the mechanism by which folic acid exerts its beneficial effect remains unknown. Folate transporter genes, including the reduced folate carrier gene (RFC1), have been proposed as NTD risk factors. METHODS: The study population included 104 nuclear families with NTDs and 100 nonmalformed control families. We investigated the possible association between a common RFC1 polymorphism (A80G) and NTD risk among offspring, as well as potential gene-environment interactions between the infant RFC1 genotype and maternal periconceptional use of folic acid through a population-based case-control study. RESULTS: We observed that the infants of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to the AA genotype (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.04-6.36) in our study population. Among mothers who did not utilize folic acid supplements, the risk for having a child with an NTD was 3.30 (95% CI, 1.15-9.65) for offspring with the GG genotype, compared to the reference (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR, 8.80; 95% CI, 2.83-28.69), compared to offspring with the AA and GA genotypes whose mothers utilized folic acid supplements. CONCLUSIONS: Our findings suggest that the RFC1 G allele is likely to be an important genetic factor in determining folate transport and subsequently may be a risk factor for NTDs in this Chinese population.     

Markers of macromolecular oxidative damage in maternal serum and risk of neural tube defects in offspring

Neural tube defects (NTDs) are among the most common and severe congenital malformations. To examine the association between markers of macromolecular oxidative damage and risk of NTDs, we measured levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), and 8-iso-prostaglandin F2α (8-iso-PGF2α) in maternal serum samples of 117 women with NTD-affected pregnancies and 121 women with healthy term newborns. We found higher levels of 8-OHdG and PC in the NTD group than in the control group; however, we did not observe a statistically significant difference in 8-iso-PGF2α levels between the NTD and the control groups. NTD risk increased with increasing quartiles of 8-OHdG [odds ratio (OR)=1.17; 95% confidence interval (CI) 0.39–3.51; OR=2.19; 95% CI, 0.68–7.01; OR=3.70; 95% CI, 1.30–10.51, for the second, third, and fourth quartile relative to the lowest quartile, respectively; P=0.009], and with increasing quartiles of PC (OR=2.26; 95% CI, 0.66–7.69; OR=3.86; 95% CI, 1.17–12.80; OR=5.98; 95% CI, 1.82–19.66, for the second, third, and fourth quartile relative to the lowest quartile, respectively; P=0.002]. Serum levels of 8-OHdG were higher in women who did not take folic acid supplements during the periconceptional period. These results suggest that oxidative stress is present in women carrying pregnancies affected by NTDs.     

The effect of fever, febrile illnesses, and heat exposures on the risk of neural tube defects in a Texas-Mexico border population

BACKGROUND: Hyperthermia produces neural tube defects (NTDs) in a variety of animal species. Elevated maternal body temperatures may also place the developing human embryo at risk. We examined the relation between maternal hyperthermia and the development of NTDs in a high-risk Mexican-American population. METHODS: Case-women were Mexican-American women with NTD-affected pregnancies who resided and delivered in any of the 14 Texas counties bordering Mexico, during 1995-2000. Control-women were randomly selected from study area residents delivering normal live births, frequency-matched to cases by hospital and year. Information on maternal fevers, febrile illnesses, exposures to heat generated from external sources, and hyperthermia-inducing activities was gathered through in-person interviews, conducted about six weeks postpartum. RESULTS: The risk effect (OR) associated with maternal fever in the first trimester, compared to no fever, was 2.9 (95% CI, 1.5-5.7). Women taking fever-reducing medications showed a lower risk effect (OR, 2.4; 95% CI, 1.0-5.6) than those who did not (OR, 3.8; 95% CI, 1.4-10.9). First-trimester maternal exposures to heat devices such as hot tubs, saunas, or electric blankets were associated with an OR of 3.6 (95% CI, 1.1-15.9). Small insignificant effects were observed for activities such as cooking in a hot kitchen (OR, 1.6; 95% CI, 1.0-2.6) and working or exercising in the sun (OR, 1.4; 95% CI, 0.9-2.2). CONCLUSIONS: Maternal hyperthermia increases the risk for NTD-affected offspring. Women intending to become pregnant should avoid intense heat exposures, carefully monitor and manage their febrile illnesses, and routinely consume folic acid supplements.     

Folate-mediated one-carbon metabolism and neural tube defects: balancing genome synthesis and gene expression

Neural tube defects (NTDs) refer to a cluster of neurodevelopmental conditions associated with failure of neural tube closure during embryonic development. Worldwide prevalence of NTDs ranges from approximately 0.5 to 60 per 10,000 births, with regional and population-specific variation in prevalence. Numerous environmental and genetic influences contribute to NTD etiology; accumulating evidence from population-based studies has demonstrated that folate status is a significant determinant of NTD risk. Folate-mediated one-carbon metabolism (OCM) is essential for de novo nucleotide biosynthesis, methionine biosynthesis, and cellular methylation reactions. Periconceptional maternal supplementation with folic acid can prevent occurrence of NTDs in the general population by up to 70%; currently several countries fortify their food supply with folic acid for the prevention of NTDs. Despite the unambiguous impact of folate status on NTD risk, the mechanism by which folic acid protects against NTDs remains unknown. Identification of the mechanism by which folate status affects neural tube closure will assist in developing more efficacious and better targeted preventative measures. In this review, we summarize current research on the relationship between folate status and NTDs, with an emphasis on linking genetic variation, folate nutriture, and specific metabolic and/or genomic pathways that intersect to determine NTD outcomes.     

Effectiveness of bivalent and quadrivalent human papillomavirus vaccination in Luxembourg

BackgroundIn Luxembourg, the human papillomavirus (HPV) vaccination program introduced in 2008, provided either bivalent (BV) or quadrivalent (QV) vaccines to girls aged 12–17 years. Here, we estimate the effectiveness of BV and QV vaccines combined and separately in reducing type-specific HPV prevalence eight years after the introduction of the vaccination program.MethodsA cross-sectional prevalence study was conducted among women aged 18–29 years in 2015-2017. Seven hundred sixteen participants were recruited at family planning centres or private gynaecology practices in Luxembourg. Vaccination records were verified in the social security database. Cervical samples were tested using the Anyplex II HPV28 assay. Vaccine effectiveness was estimated using logistic regression.ResultsIn total, 363/716 (50.7%) participants were HPV positive with any HPV and 209/716 (29.2%) with carcinogenic HPV genotypes. HPV vaccination offered high protection against HPV16/18 (adjusted odds ratio (AOR) = 0.13; 95% CI 0.03-0.63), HPV6/11 (AOR = 0.16; 95% CI 0.05-0.48) and cross-protection against HPV31/33/45 (AOR = 0.41; 95% CI 0.18-0.94). The AORs were generally enhanced when only considering vaccination before sexual debut corresponding to AORs: 0.05 (95% CI 0.00-0.88), 0.08 (95% CI 0.02-0.36) and 0.20 (0.06-0.65) against HPV16/18, HPV6/11 and HPV31/33/45, respectively. We observed significant protection against carcinogenic genotypes included in nonavalent vaccine for BV (AOR = 0.29; 95% CI 0.13-0.67), but not for QV (AOR = 0.81; 95% CI 0.47–1.40) (heterogeneity Chi² P = 0.04).ConclusionsOur study suggests high effectiveness of HPV vaccination against HPV6/11, HPV16/18 and a cross-protection against HPV31/33/45. Vaccination effectiveness was slightly higher for women vaccinated before sexual debut.     

Higher serum homocysteine and lower thyroid hormone levels in pregnant women are associated with neural tube defects

BackgroundThis study tested the hypothesis that abnormal maternal metabolism of both homocysteine and thyroid hormone network in pregnant women is associated with neural tube defects (NTDs) in a part of China with high NTD prevalence.MethodsA case–control study was performed between 2007 and 2009 in Lüliang Mountains, Shanxi Province. This study included 83 pregnant women who had fetuses with NTDs (cases) and 90 pregnant women with normal fetuses (controls). In addition, a cell model to illustrate the epidemiological findings was established.ResultsFetuses of mother who had both high total homocysteine (tHcy) and inadequate free thyroxine were 3 times more at risk of developing NTDs (adjusted odds ratio = 3.5; 95 % confidence interval = 1.2–10.4; cases vs. controls) using multivariate logistic regression models. Furthermore, biological interaction between metabolisms of Hcy and thyroid hormones was demonstrated in vitro. In homocysteine thiolactone of a metabolite of Hcy-treated mouse embryonic neural stem NE4C cells, genes (Bmp7, Ctnnb1, Notch 1, Gli2, and Rxra) related to both neural tube closure and thyroid hormone network were shown to be regulated by H3K79 homocysteinylation, which increased their expression levels.ConclusionsThe effect of maternal serum high tHcy on risk of developing NTDs is depended on maternal serum level of thyroxine. Meanwhile, a higher level of tHcy might also affect both maternal metabolism of thyroid hormone and neural tube closure in embryogenesis through homocysteinylation of histones.     

Comorbidities and Lack of Blood Transfusion May Negatively Affect Maternal Outcomes of Women with Obstetric Hemorrhage Treated with NASG

The Non-Pneumatic Anti-Shock Garment (NASG) is a first-aid device to reduce mortality from severe obstetric hemorrhage, the leading cause of maternal mortality globally. We sought to evaluate patient characteristics associated with mortality among a cohort of women treated with the NASG in Nigeria. Data on 1,149 women were collected from 50 facilities participating in the Pathfinder International Continuum of Care: Addressing Postpartum Hemorrhage project in Nigeria from 2007–2012. Characteristics were compared using the appropriate distributional tests, and we estimated multivariable logistic regression models to control for treatment received. There were 201 deaths (17.5%). Women who died were significantly more likely to have any co-morbidity (AOR 3.63, 95% CI: 2.41–5.48), ruptured uterus (AOR 2.79, 95% CI: 1.48–5.28), macerated stillbirth (AOR 2.96, 95% CI 1.60–5.48) and to have had 6 or more previous births, (AOR 1.53, 95% CI 1.11–2.12), after adjusting for treatment received. These results suggest certain maternal conditions, particularly the presence of another life-threatening co-morbidity or macerated stillbirth, conferred a higher risk of mortality from PPH. This underscores the need for multi-system assessment and a comprehensive approach to the treatment of women with pregnancy complications.     

Differences in risk factors for head and neck cancer among men and women in Nepal: A case-control study

BackgroundHead and neck cancer (HNC) is a major cause of cancer morbidity and mortality in Nepal. The study aims to investigate differences in risk factors for head and neck cancer by sex in Nepal.MethodsA hospital-based case-control study was conducted at the B.P. Koirala Memorial Cancer Hospital in Nepal from 2016 to 2018. A semi-structured questionnaire consisting of socio-demographic characteristics, dietary habits, reproductive factors, household air pollution, tobacco use (smoking and chewing), alcohol consumption, and second-hand smoking was used to collect the data. Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders.ResultsA total of 549 HNC cases (438 men and 111 women) and 601 age-matched healthy controls (479 men and 122 women) were recruited in this study. An increased risk of HNC for low education level and family income were observed among men (adjusted odds ratio (AOR) for 3rd grade and less= 1.58, 95 % CI= 1.14–2.18; AOR for family monthly income < 5000 Rupees = 1.64, 95 % CI 1.20–2.24). The AORs among women were higher than the men for known risk factors (AOR for smoking 1.34 (95 % CI 0.96–1.86) for men, 2.94 (95 % CI 1.31–6.69) for women; AOR for tobacco chewing 1.76 (95 % CI 1.27–2.46) for men, 10.22 (95 % CI 4.53–23.03) for women).ConclusionOur results point to an effect modification by sex for HNC risk factors with high AORs observed among women.     

Decline in the prevalence of neural tube defects following folic acid fortification and its cost-benefit in South Africa

BACKGROUND: In October 2003 South Africa embarked on a program of folic acid fortification of staple foods. We measured the change in prevalence of NTDs before and after fortification and assessed the cost benefit of this primary health care intervention. METHODS: Since the beginning of 2002 an ecological study was conducted among 12 public hospitals in four provinces of South Africa. NTDs as well as other birth defect rates were reported before and after fortification. Mortality data were also collected from two independent sources. RESULTS: This study shows a significant decline in the prevalence of NTDs following folic acid fortification in South Africa. A decline of 30.5% was observed, from 1.41 to 0.98 per 1,000 births (RR = 0.69; 95% CI: 0.49–0.98; p = .0379). The cost benefit ratio in averting NTDs was 46 to 1. Spina bifida showed a significant decline of 41.6% compared to 10.9% for anencephaly. Additionally, oro‐facial clefts showed no significant decline (5.7%). An independent perinatal mortality surveillance system also shows a significant decline (65.9%) in NTD perinatal deaths, and in NTD infant mortality (38.8%). CONCLUSIONS: The decrease in NTD rates postfortification is consistent with decreases observed in other countries that have fortified their food supplies. This is the first time this has been observed in a predominantly African population. The economic benefit flowing from the prevention of NTDs greatly exceeds the costs of implementing folic acid fortification. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies

BACKGROUND: This study examined the association between maternal smoking and alcohol use (including binge drinking) during the periconceptional period (i.e., 2 months before through 2 months after conception) and the risk of orofacial clefts, NTDs, and conotruncal heart defects in offspring. METHODS: Data were drawn from a population‐based case‐control study of fetuses and live‐born infants among a cohort of California births between July 1999 and June 2003. The 1,355 cases comprised of 701 orofacial clefts, 337 NTDs, and 323 conotruncal heart defects. Information on smoking and alcohol consumption was obtained via telephone interviews with mothers of 1,355 (80% of eligibles) cases and 700 (77% of eligibles) nonmalformed, live‐born controls. RESULTS: Maternal smoking of five cigarettes or less per day was associated with reduced risks of NTDs (OR 0.7; 95% CI: 0.3, 1.4), whereas the risk associated with higher cigarette consumption was lower for conotruncal heart defects (OR 0.5; 95% CI: 0.2, 1.2). Maternal intake of alcohol less than 1 day per week was associated with a 1.6‐ to 2.1‐fold higher risk of NTDs (95% CI: 0.9, 2.6), d‐transposition of the great arteries (95% CI: 1.1, 3.2), and multiple cleft lip with or without cleft palate (CLP) (95% CI: 0.8, 4.5). Risks associated with more frequent alcohol intake were 2.1 for NTDs (95% CI: 1.1, 4.0) and 2.6 for multiple CLP (95% CI: 1.1, 6.1). CONCLUSIONS: This study observed that maternal alcohol intake increased the risk for d‐transposition of the great arteries, NTDs, and multiple CLP in infants. By contrast, smoking was associated with a lower risk of NTDs and conotruncal heart defects. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Maternal zinc and fetal neural tube defects.

Among the factors implicated in the heterogeneous etiology of neural tube defects (NTDs) is the trace element zinc (Zn). In a case-control study, we collected midtrimester maternal toenail samples for multiple trace element analyses, including Zn, which were assayed by neutron activation analysis. We studied 17 women with NTD offspring and 1,787 controls. The crude OR for NTD comparing Zn values greater than normal range to normal Zn values was 3.2 (95% CI 1.1,9.7). These results were not materially affected when adjustment was made for folic acid supplementation. An overall increased risk for NTD associated with increasing toenail Zn was also evident. A matched subset of 17 cases and 73 controls yielded a crude OR of 3.1 (95% CI 0.9,10.3) when cases with elevated Zn (greater than or equal to 120 ppm) were compared to those with normal Zn. Matched analyses controlling for folic acid supplements, family history of NTD, assay batch, age of mother and year of delivery yielded an OR of 5.0 (95% CI 1.1,21.6). This study reveals an association between increased toenail Zn in the second trimester of pregnancy and the risk of having a child with an NTD. Whether Zn sequestration has resulted in relative Zn deficiency at the site of neural tube closure remains uncertain.     

Maternal and Neonatal Mortality in South-West Ethiopia: Estimates and Socio-Economic Inequality

Introduction

Ethiopia has achieved the fourth Millennium Development Goal by reducing under 5 mortality. Nevertheless, there are challenges in reducing maternal and neonatal mortality. The aim of this study was to estimate maternal and neonatal mortality and the socio-economic inequalities of these mortalities in rural south-west Ethiopia.

Methods

We visited and enumerated all households but collected data from those that reported pregnancy and birth outcomes in the last five years in 15 of the 30 rural kebeles in Bonke woreda, Gamo Gofa, south-west Ethiopia. The primary outcomes were maternal and neonatal mortality and a secondary outcome was the rate of institutional delivery.

Results

We found 11,762 births in 6572 households; 11,536 live and 226 stillbirths. There were 49 maternal deaths; yielding a maternal mortality ratio of 425 per 100,000 live births (95% CI:318–556). The poorest households had greater MMR compared to richest (550 vs 239 per 100,000 live births). However, the socio-economic factors examined did not have statistically significant association with maternal mortality. There were 308 neonatal deaths; resulting in a neonatal mortality ratio of 27 per 1000 live births (95% CI: 24–30). Neonatal mortality was greater in households in the poorest quartile compared to the richest; adjusted OR (AOR): 2.62 (95% CI: 1.65–4.15), headed by illiterates compared to better educated; AOR: 3.54 (95% CI: 1.11–11.30), far from road (≥6 km) compared to within 5 km; AOR: 2.40 (95% CI: 1.56–3.69), that had three or more births in five years compared to two or less; AOR: 3.22 (95% CI: 2.45–4.22). Households with maternal mortality had an increased risk of stillbirths; OR: 11.6 (95% CI: 6.00–22.7), and neonatal deaths; OR: 7.2 (95% CI: 3.6–14.3). Institutional delivery was only 3.7%.

Conclusion

High mortality with socio-economic inequality and low institutional delivery highlight the importance of strengthening obstetric interventions in rural south-west Ethiopia.     

Khat Chewing and Restrictive Dietary Behaviors Are Associated with Anemia among Pregnant Women in High Prevalence Rural Communities in Eastern Ethiopia

Background

Anemia affects a high proportion of pregnant women in the developing countries. Factors associated with it vary in context. This study aimed to determine the prevalence and predictors of anemia among pregnant women in the rural eastern Ethiopia.

Methods

A community-based cross-sectional study was done on 1678 pregnant women who were selected by a cluster random sampling technique. A pregnant woman was identified as anemic if her hemoglobin concentration was <11 g/dl. Data were collected in a community-based setting. Multilevel mixed effect logistic regression was used to determine the adjusted odds ratios (AOR) with 95% confidence intervals (CI) for the predictors of anemia.

Results

Anemia was observed among 737(43.9%) of the 1678 pregnant women studied (95% CI 41.5%–46.3%). After controlling for the confounders, the risk of anemia was 29% higher in the women who chewed khat daily than those who sometimes or never did so (AOR, 1.29; 95% CI, 1.02–1.62). The study subjects with restrictive dietary behavior (reduced either meal size or frequency) had a 39% higher risk of anemia compared to those without restrictive dietary behavior (AOR, 1.39; 95% CI, 1.02–1.88). The risk of anemia was increased by 68% (AOR, 1.68; 95% CI, 1.15–2.47), and 60% (AOR, 1.60; 95% CI, 1.08–2.37) in parity levels of 2 births and 3 births, respectively. Compared to the first trimester, the risk of anemia was higher by two-fold (AOR, 2.09; 95% CI, 1.46–3.00) in the second trimester and by four-fold (AOR, 4.23; 95% CI, 2.97–6.02) in the third trimester.

Conclusion

In this study, two out of five women were anemic. Chewing khat and restrictive dietary habits that are associated with anemia in the setting should be addressed through public education programs. Interventions should also focus on the women at higher parity levels and those who are in advanced stages of pregnancy.     

Periconceptional dietary intake of myo-inositol and neural tube defects in offspring

BACKGROUND: Periconceptional intake of nutrients in addition to folic acid may contribute to neural tube defect (NTD) etiologies; a likely candidate is myo-inositol. We investigated whether maternal periconceptional dietary intake of myo-inositol influenced NTD risk. METHODS: Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. Interviews were conducted with mothers of 454 NTD cases and with mothers of 462 nonmalformed controls. A standard 100-item food frequency questionnaire was used to assess nutrient intake. RESULTS: We observed small increases in risk, with increases slightly more evident for anencephaly, associated with intakes of myo-inositol less than the highest intake quartile, e.g., risk of anencephaly was 1.3 (0.7-2.4) among fetuses whose mothers consumed lowest versus highest intakes of myo-inositol. These small increases, however, were imprecise, and also did not indicate increasing risk with decreasing level of myo-inositol intake. Adjusted risk estimates did not differ considerably from their unadjusted counterparts. CONCLUSIONS: Our results do not indicate that myo-inositol intake, as measured in this study, is strongly associated with risk of human NTDs.     

Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies

Background

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs.

Methods

An electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis.

Results

A significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis ( TT versus CC: OR  = 2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR  = 1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR  = 1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR  = 1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls.

Conclusion

The results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted.     

The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother

Recent reports have implicated the "thermolabile" (T) variant of methylenetetrahydrofolate reductase (MTHFR) in the causation of folate-dependent neural tube defects (NTDs). We report herein the largest genetic study of NTD cases (n=271) and families (n=218) to date, establishing that, in Ireland, the "TT" genotype is found in 18.8% of cases versus 8.3% of controls (odds ratio 2.57; confidence interval [CI] 1.48-4.45; P=.0005). The maternal and paternal TT genotypes have intermediate frequencies of 13.8% and 11.9%, respectively, indicating that the predominant MTHFR-related genetic effect acts via the TT genotype of the developing embryo. Analysis of the 218 family triads of mother, father, and affected child with log-linear models supports this interpretation, providing significant evidence that the case TT genotype is associated with NTDs (P=.02) but no evidence of a maternal TT genotypic effect (P=. 83). The log-linear model predicted that the risk of NTDs conferred by the case TT genotype is 1.61 (CI 1.06-2.46), consistent with the paramount importance of the case TT genotype in determining risk. There is no compelling evidence for more than a modest additional risk conferred by a maternal TT genotype. These results favor a biological model of MTHFR-related NTD pathogenesis in which suboptimal maternal folate status imposes biochemical stress on the developing embryo, a stress it is ill-equipped to tolerate if it has a TT genotype.     

Folate status and neural tube defects

Periconceptional folic acid supplementation prevents approximately 70% of neural tube defects (NTDs). While most women carrying affected fetuses do not have deficient blood folate levels, the risk of having an NTD affected child is inversely correlated with pregnancy red cell folate levels. Current research is focused on the discovery of genetic abnormalities in folate related enzymes which might explain the role of folate in NTD prevention. The first candidate gene to emerge was the C677T variant of 5,10-methylenetetrahydrofolate reductase. Normal subjects who are homozygous for the mutation (TT) have red cell folate status some 20% lower than expected. It is now established that the prevalence of the TT genotype is significantly higher among spina bifida cases and their parents. Nevertheless, our studies show that the variant does not account for the reduced blood folate levels in many NTD affected mothers. We conclude that low maternal folate status may in itself be the most important risk factor for NTDs and that food fortification may be the only population strategy of benefit in the effort to eliminate NTDs.